Polycystic kidney disease

Abstract

Polycystic kidney disease (PKD) is a group of monogenic disorders that result in renal cyst development, progressive chronic kidney disease, and are associated with extrarenal manifestations. The most common form, autosomal dominant PKD (ADPKD), is a multisystem disease most often diagnosed in adults and caused by mutations in PKD1 and PKD2. The PKD1 gene product, polycystin-1 (PC1), is a large receptor like protein. The PKD2 gene product, polycystin-2 (PC2)' is a member of the transient receptor potential family (i.e., TRPP2) and is a nonselective cation channel that is permeable to calcium. Both PC1 and PC2 are located on non-motile cilia located on virtually all epithelia and other cell types.Autosomal recessive PKD (ARPKD) usually presents during infancy with enlarged kidneys and hepatic fibrosis, but patients are increasingly being identified during childhood and early adulthood. ARPKD is caused by mutations in PKHD1. The protein encoded by this gene, polyductin, is localized to the basal body of non-motile cilia and can form a complex with PC2.Molecular genetic testing plays an increasingly important role in the management of PKD. In ADPKD, testing enables early diagnosis of patients with inconclusive results by kidney imaging; this can clarify the disease status of a prospective related kidney donor. In both ADPKD and ARPKD, testing can inform pre-implantation genetic diagnosis (PGD). The purpose of this chapter is to review the clinical and laboratory characteristics of these disorders and to describe the application of emerging molecular technologies.